Background: Alterations in cognitive/affective/sleep functioning are among the most challenging side effects experienced by 80% of patients with metastatic melanoma (MM) or metastatic renal cell carcinoma (MRCC) undergoing high dose Interleukin-2 (IL-2) therapy.1 Altered cognition2 includes a wide array of symptoms such as alterations in concentration, attention, short-term memory, confusion, mental fatigue, executive functioning, abstraction, language, basic arithmetic and orientation;3,4 affective symptoms2 include mood alterations, depression, anxiety, psychosis, hallucinations, aggression, suicide ideation and coma;5-7 and sleep symptoms include insomnia (initial, middle, delayed) and hypersomnia.8 Methods: This exploratory, descriptive, mixed methods case study design will describe the trajectory of transient and residual cognitive/affective/sleep symptoms in ten high-dose IL-2 cases. Each IL-2 case consists of the IL-2 patient, care partner, and primary nurse. Through case study analyses, qualitative data from the care partner and nurse will be synthesized with qualitative and quantitative data from the patient to inform and describe the patterns of cognitive/affective/sleep symptoms experienced by the patient during treatment. The specific aims of this study are to: Aim 1) Describe transient and residual cognitive (language, concentration, confusion, attention, short-term memory, and orientation), affective (depression, anxiety, mood alterations), and sleep (insomnia, hypersomnia) symptoms in patients during up to four hospitalizations for high-dose IL-2 therapy. Aim 2) Describe patient transient and residual cognitive/affective/sleep symptoms as qualitatively reported by each patient's care partner, and primary nurse during each hospital admission for IL-2 therapy. Aim 3) Describe the trajectory of transient and residual cognitive/affective/sleep symptoms in IL-2 patients over the total number of hospitalizations, synthesizing patient data with care partner and nurse reports of symptom change. Significance: This will be the first study to describe IL-2-induced cognitive/affective/sleep symptoms longitudinally from the perspective of the individuals experiencing the treatment course: the patient, their care partner, and their nurse. These individuals will describe the trajectory, duration and severity of these symptoms through journaling, interviews, and cognitive/affective/sleep measures. Results from this study will identify critical time points along the symptom trajectory to target interventions. These data will inform future interventional studies that help patients during periods of aggressive medical treatment, supporting their care partners, and nurses.